Identification of the key ferroptosis-related genes in the pathogenesis of thoracic aortic dissection and thoracic aortic aneurysm using integrated bioinformatic analysis and experimental verification

Abstract

Abstract Background Thoracic aortic dissection (TAD) and thoracic aortic aneurysm (TAA) are interrelated diseases, but there is no evidence of a relationship between ferroptosis and the common pathogenesis of TAD and TAA. To investigate the potential target of inhibiting TAD/TAA, we identified the key ferroptosis-related genes in the pathogenesis of TAD/TAA through integrated bioinformatic analysis and experimental verification. Results A total of 263 common differentially expressed genes (DEGs) were found between normal and TAD/TAA datasets. In the functional enrichment of DEGs, immune-related and inflammation-related pathways dominated. Moreover, eight key ferroptosis-related genes were identified and verified. Western blot and qRT-PCR results showed that HIF1A, SAT1, ARNTL and DDIT4 were significantly differentially expressed in normal and TAD/TAA aortic tissues. Finally, these key genes in vascular smooth muscle cells were validated in erastin-induced ferroptosis model and macrophage co-culture model. Our finding suggests these key ferroptosis-related genes were activated in the process of ferroptosis and participated in the regulation of ferroptosis during macrophage infiltration. Conclusions HIF1A, SAT1, ARNTL and DDIT4 were identified as key ferroptosis-related genes and play a central role in both TAA and TAD. These findings will provide us with new insight into the mechanisms of ferroptosis in TAD/TAA and suggest therapeutic targets to inhibit the progression of TAD/TAA.